Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000638179 | SCV000759665 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2017-10-30 | criteria provided, single submitter | clinical testing | This variant, c.405_407delAGT, results in the deletion of 1 amino acid of the MPZ protein (p.Ile135_Val136delinsMet), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MPZ-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. Different missense substitutions at these codons (p.Ile135Thr, p.Ile135Met, p.Ile135Leu, p.Val136Glu) have been reported in individuals and families affected with Dejerine-Sottas syndrome and Charcot-Marie-Tooth disease (PMID: 11835375, 22018721, 8664899, 8797476). This suggests that the isoleucine and valine residues are critical for MPZ protein function and that a deletion of these codons may also be pathogenic. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |